cholesterol

hepatology coverResearchers have identified a microRNA liver gene, miR-27b, which regulates lipid (cholesterol or fat) levels in the blood. This regulator gene controls multiple genes involved in dyslipidemia—abnormal blood cholesterol levels that can contribute to heart disease. Study details published in the February issue of Hepatology, a journal of the American Association for the Study of Liver Diseases (AASLD), describe a new in silico approach to identify the significance of microRNAs in regulating disease-related gene pathways.

The Human Genome Project (HGP) was completed in April, 2003 and the world had a map of the 3 billion DNA letters making up the human genome. One of the HGP leaders was Dr. Francis Collins, currently NIH Director and contributor to the present study. “The HGP provided the basic instruction book for human biology,” explains Dr. Collins. “Further genomic studies, such as the investigation of microRNAs, have built upon the efforts of the HGP to explain how the genome carries out its functions, and helps identify genes involved in the development of disease.”

For the present study, lead author Dr. Kasey Vickers from the NIH/NHLBI Lipoprotein Metabolism Section (presently at Vanderbilt University School of Medicine) and colleagues performed high-throughput small RNA sequencing of mouse liver and detected roughly 150 microRNAs. The team used a novel in silico approach to identify microRNA regulatory hub genes involved in lipid metabolism. In human and mouse livers miR-27b was determined to be the strongest hub with 27 predicted targets.

“We found liver miR-27b levels to be sensitive to high triglycerides (hyperlipidemia) in the blood and liver,” said Dr. Vickers. The team reported a nearly 3-fold increase in miR-27b levels in [click to continue…]

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  • New publication in Nature shows therapeutic silencing of microRNA-33a/b for atherosclerosis:
    Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides
    K.J. Rayner et al.
    Nature 478, 404–407 (20 October 2011)
    http://www.nature.com/nature/journal/v478/n7369/full/nature10486.html

    Pre-clinical Data on miR-133
  • Regulus Therapeutics and Collaborators Publish New Pre-Clinical Data on microRNA-33 Demonstrating Key Role in Cholesterol Homeostasis and Fatty Acid Metabolism
  • Company to host webinar on October 26, 2011 to discuss findings

regulus therapeutics logoLA JOLLA, Calif., Oct. 20, 2011 /PRNewswire/ — Regulus Therapeutics Inc., a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, and collaborators at NYU Langone Medical Center and Wake Forest Baptist Medical Center today announced the publication of new pre-clinical research findings in the journal Nature (Rayner et al., Nature, October 20, 2011). The new data show the first demonstration of marked increases in high density lipoprotein cholesterol (HDL-C), the ‘good’ cholesterol, and suppression of plasma triglyceride levels in non-human primates through inhibition of both microRNA-33a and microRNA-33b (miR-33a/b) with proprietary chemically modified anti-miR oligonucleotides. A webinar to discuss the new data will be hosted by Regulus and features Kathryn Moore, Ph.D., associate professor in the Department of Medicine at NYU Langone Medical Center and Regulus scientists (11:00am EDT, October 26, 2011).

“In addition to atherosclerotic plaque regression and enhanced reverse cholesterol transport that we previously observed in rodents with our collaborators at NYU Langone Medical Center, anti-miR-33 treatment is now shown to [click to continue…]

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Research Article

Katey J. Rayner, Frederick J. Sheedy, Christine C. Esau, Farah N. Hussain, Ryan E. Temel, Saj Parathath, Janine M. van Gils, Alistair J. Rayner, Aaron N. Chang, Yajaira Suarez, Carlos Fernandez-Hernando, Edward A. Fisher, Kathryn J. Moore
J. Clin. Invest. 2011; doi:10.1172/JCI57275

Regulus Therapeutics and Collaborators from NYU Langone Medical Center Publish New Data Demonstrating Clearance of Cholesterol from Bloodstream and Reduction of Atherosclerotic Plaques through Inhibition of microRNA-33

- Paper published in Journal of Clinical Investigation supports development of anti-microRNA 33 as potential therapeutic for atherosclerosis and related metabolic diseases -

LA JOLLA, Calif., June 6, 2011 – Regulus Therapeutics Inc., a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today announced publication in the Journal of Clinical Investigation of new pre-clinical data in mice on the antagonism of microRNA-33 (miR-33). The study, performed with collaborators at NYU Langone Medical Center, demonstrated that antagonism of miR-33 with proprietary chemically modified anti-miR oligonucleotides can promote clearance of excess cholesterol and statistically significant regression of atherosclerosis in mice with established atherosclerotic plaques.

Recent advances in lipid metabolism have identified miR-33 as a “master switch” of cholesterol transport genes, such as ATP-binding cassette transporter A1 (ABCA1), a regulator of high density lipoprotein cholesterol (HDL-C), or ‘good’ cholesterol. Inhibition of miR-33 results in increased ABCA1 expression and elevations in HDL-C, suggesting that miR-33 antagonism may be [click to continue…]

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